EFFECTS OF NEURONAL NO SYNTHASE (nNOS) INHIBITION ON THE ACTIVATION OF RENAL MECHANOSENSORY NEURONS

	EFFECTS OF NEURONAL NO SYNTHASE (nNOS) INHIBITION ON THE ACTIVATION OF RENAL MECHANOSENSORY NEURONS
Research field:	Kidney physiology
Authors:	Kopp UC, Cicha MZ, Smith LA, Hökfelt T
Address of presenting author:	Department of Internal Medicine, VA Medical Center & University of Iowa College of Medicine, Iowa City, IA 52242, USA
E-mail:	ukopp@blue.weeg.uiowa.edu
Phone:	(319) 338-0581
Fax:	(319) 339-7023
Text of abstract	Introduction In the rat kidney, the majority of the sensory neurons containing substance P are located in the renal pelvic wall (Liu & Barajas, 1993). Increasing renal pelvic pressure by high urine flow rate or acute ureteral obstruction increases renal pelvic pressure, stretches the renal pelvic wall and activates mechanosensitive neurons in the pelvic wall. Activation of these neurons leads to increases in ipsilateral afferent renal nerve activity (ARNA) and contralateral urinary sodium excretion, a renorenal reflex response. Our studies have shown that the ARNA response to increased renal pelvic pressure is due to release of substance P from the renal pelvic sensory nerves (Kopp et al. 2000). Nitric oxide (NO) is a known neuromodulator (Zanzinger, 1999). nNOS has been localized in neurons in the renal pelvic wall (Bachmann et al. 1995). However, it is not known whether these neurons are of sensory origin. We now examined if nNOS is colocalized with substance P in renal pelvic nerves and dorsal root ganglion (DRG) neurons at T10-L1 which contain the cell bodies of afferent renal nerves. We also examined if the ARNA response to increased renal pelvic pressure was altered by an inhibitor of NOS, L-NAME, and/or a selective inhibitor of nNOS, S-methyl-L-thiocitrulline (L-SMTC, Furfine et al. 1994). Methods Immunohistochemistry was performed using antisera against goat nNOS and rabbit substance P. Renal pelvic pressure was increased 15 mmHg for 3 min in anesthetized rats before and during renal pelvic perfusion with either L-NAME, 5 mM, or L-SMTC, 20 mM. Substance P was measured by ELISA. Results nNOS was colocalized with substance P in the renal pelvic nerves and DRG (T10-L1), suggesting that nNOS is localized in renal sensory nerves. L-NAME and L-SMTC produced similar enhancement of the ARNA response to increased renal pelvic pressure. The ARNA response was 116±28% x min (area under the curve: ARNA vs min) before and 413±73% x min during L-SMTC (P<0.02, n=7). The enhanced ARNA response was entirely due to a prolongation of the ARNA response, the duration of the response being 4.8±0.5 min before and 24±3 min during L-SMTC. L-SMTC did not alter the increase in renal pelvic release of substance P produced by increased renal pelvic pressure, the increase in substance P release being 9.5±5.5 pg/min before 10.4±3.4 pg/min during L-SMTC. Conclusions nNOS is localized in renal pelvic sensory nerves. Inhibition of nNOS enhances the ARNA response to increased renal pelvic pressure by a mechanism distal to the release of substance P. These data suggest that NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensitive neurons. References Liu, L. & Barajas, L. 1993. Anat Embryol 188,345-361 Kopp, U.C., Farley, D.M., Cicha, M.Z. & Smith, L.A. 2000. Am J Physiol 278,R937-R946 Zanzinger, J. 1999. Cardiovasc Res 43, 639-649 Bachmann, S., Bosse, H.M. & Mundel, P. 1995. Am. J Physiol 268, F885-F898 Furfine, E.S., Harmon, M.F., Paith, J.E., Knowles, R.G., Salter, M., Kiff, R.J., Duffy, C., Hazelwood, R., Oplinger, J.A. & Garvey, E.P. 1994. J Biochem 269, 26677-26683
Keywords:	renal nerves, nitric oxide, kidney, substance P, DRG

Created 2000-04-20